Two aspects of the cytotoxic T lymphocyte response to influenza virus will be studied in this proposal. We will examine the heterogeneity and specificity of the cytotoxic T lymphocyte response to specific type A influenza virion antigens with the aim of assessing, from a functional standpoint, the concept that the antigen recognition structures employed by thymus-derived (T) and bone marrow-derived (B) lymphocytes are in part at least shared by the two lymphocyte types. The basic protocol will be to stimulate in vitro cytotoxic T lymphocyte responses from previously primed precursor cells using purified influenza virion antigens. The overall specificity and heterogeneity of the cytotoxic T cells so generated will be examined using target cells infected with appropriate influenza virus strains. The fine specificity of recognition by influenza hemagglutinin will be examined using virus strains with serologically cross-reactive hemagglutinins. This examination will also include an in vitro analysis of the response of individual cytotoxic T lymphocyte precursors directed to influenza hemagglutinin. The second part of this proposal deals with viral antigen presentation in the induction of influenza virus-specific cytotoxic T lymphocytes and in the process of target cell sensitization for lysis by influenza virus-specific cytotoxic T lymphocytes. Specifically we will examine whether the presentation of influenza viral antigens in a specific fashion i.e. as integral membrane components of the stimulator and target cell cytoplasmic membrane, is required for induction and target cell sensitization. Stimulator cells or target cells will be exposed to influenza virions or to influenza hemagglutinin under a variety of conditions and their respective capacities to induce cytotoxic T lymphocyte responses or to be rendered susceptible to T cell mediated lysis will be assessed.